The role of nonenzymatic glycosylation of both structural and enzymatic proteins in the biochemistry of diabetic sequelae of the lens and peripheral nerve is being examined. Modification of lens crystallins by hexose in the diabetic and galactosemic rat is associated with the formation of high molecular weight aggregates, disulfide bond formation and an increased scattering of light. This mechanism is much the same as proposed for the human diabetic or senile cataract. Yellow Maillard reaction products of crystallins glycosylated in vitro have the same fluorescent maxima and spectral pattern as chromophores isolated from human cataracts. The formation of light scattering aggregates of crystallin in the hyperglycemic rat are associated with a loss of glutathione and other antioxidants and in increased cell membrane permeability. The protective role of reducing agents and antioxidants in opposing cataract formation is being investigated. Both reversible and stable modifications of enzymes concerned with glutathione metabolism are being investigated under hyperglycemic conditions. The lens and Schwann cell share a loss of small molecules in diabetes. Results on the maintenance of reducing equivalence, antioxidant properties and cell permeability in the lens are therefore being examined for their role in the peripheral neuropathy of the diabetic rat.